It is proposed to investigate the pharmacological and biochemical properties as well as certain functional interrelationships of Cebus and rhesus monkey brain monoaminergic systems that might serve as sites of action for antipsychotic drugs, hallucinogens and also certain other related CNS-active drugs. The approach is based on our previous work indicating the presence of three pharmacologically distinct types of dopamine receptors associated with adenylate cyclase in different regions of monkey brain and also the presence of mescaline-, lysergic acid diethylamide- and serotonin-stimulated activity in one of these regions, the anterior limbic cortex. Emphasis will be on the anterior limbic cortex which is particularly sensitive to antipsychotic and hallucinogenic drugs and on the frontal cortex aminergic systems. Primary auditory cortex is also responsive to hallucinogens, and this region as well as visual cortex and amygdala will also be examined and properties compared with those of caudate nucleus and the other cortical areas. Receptor binding and transmitter uptake and release studies will be included, as will certain aspects of the relationships of dopamine to histamine-beta- and alpha-adrenergic, GABA, acetylcholine and Substance P systems. Receptor supersensitivity following chronic treatment with neuroleptic drugs in vivo and desensitization following exposure of tissue in vitro to amine transmitters will be examined. These studies of primate brain monoamine systems should be of direct value in understanding brain mechanism involved in mental illness as well as in the development of more selective and possibly new approaches to treatment.